title: Post-transcriptional inhibition of hepatitis C virus replication through small interference RNA.
abstract: BACKGROUND
  Hepatitis C Virus (HCV) infection is a major health problem throughout world that causes acute and chronic infection which resulted in liver fibrosis, hepatocellular carcinoma and death. The only therapy currently available for HCV infection is the combination of pegylated interferon alpha (PEG-IFN α) and ribavirin. This therapy can effectively clear the virus infection in only 50% of infected individuals. Hence, there is a dire need to develop antiviral agents against HCV.
  
  
  RESULTS
  This study was design to examine the ability of exogenous small interfering RNAs (siRNAs) to block the replication of HCV in human liver cells. In the present study six 21-bp siRNAs were designed against different regions of HCV non-structural genes (NS2, NS3 serine protease/helicase, NS4Band NS5B RNA dependent RNA polymerase). siRNAs were labeled as NS2si241, NS3si-229, NS3si-858, NS4Bsi-166, NS5Bsi-241 and NS5Bsi-1064. We found that siRNAs against HCV NS2- NS5B efficiently inhibit HCV replication in Huh-7 cells. Our results demonstrated that siRNAs directed against HCV NS3 (NS3si-229 and NS3si-858) showed 58% and 88% reduction in viral titer respectively. Moreover, NS4Bsi-166 and NS5Bsi-1064 exhibited a dramatic reduction in HCV viral RNA and resulted in greater than 90% inhibition at a 20 μM concentration, while NS2si-241 showed 27% reduction in viral titer. No significant inhibition was detected in cells transfected with the negative control siRNA.
  
  
  CONCLUSIONS
  Our results suggest that siRNAs targeting against HCV non-structural genes (NS2-NS5B) efficiently inhibit HCV replication and combination of these siRNAs of different targets and interferon will be better option to treat HCV infection throughout the world.
authors.affiliation: Division of Molecular Medicine, National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan. usmancemb@gmail.com
authors.forename: Usman
authors.initials: U
authors.lastname: Ali Ashfaq
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ansar
authors.forename: Muhammad Tahir
authors.initials: MT
authors.lastname: Sarwar
authors.forename: Tariq
authors.initials: T
authors.lastname: Javed
authors.forename: Sidra
authors.initials: S
authors.lastname: Rehman
authors.forename: Sheikh
authors.initials: S
authors.lastname: Riazuddin
mesh_terms: D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D006526:Hepatitis C / Q000188:drug therapy / Q000235:genetics* / Q000821:virology*; D006801:Humans; D034622:RNA Interference / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics* / Q000627:therapeutic use; D014158:Transcription, Genetic / Q000187:drug effects; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
chemical_list: D034741:RNA, Small Interfering; D014764:Viral Proteins